The mechanisms of synaptic transmission and their modification with use have become a major focus of research in neuroscience. Numerous approaches have clearly demonstrated that modulation of synaptic transmission is intrinsic to such phenomena as learning and memory, neural development, and the function of neural systems in general. Understanding the mechanisms of use-dependent changes in synaptic transmission will be critical for dealing with health-related problems such as drug abuse, mental illnesses, aging and various paralytic diseases. Although much of what we know about the synapse derives from studies of the neuromuscular junction, the past several years have seen enormous strides in our understanding of synaptic transmission in the central nervous system. This Keystone Symposium will focus on those cellular and molecular aspects of synaptic transmission that have led the way in moving the field from the neuromuscular junction to the central nervous system. In eleven sessions, the conference will address many of the mechanisms involved in pre and postsynaptic function, their modification with use, and their role in development of neural pathways. Topics to be discussed include the mechanisms of neurotransmitter release, termination of transmitter activity, structure, function, and synaptic distribution of neurotransmitter receptors, the role of extracellular matrix molecules in synaptogenesis, second message regulation of synaptic transmission, synaptic regulation of gene expression, and use-dependent modification of synaptic structure and function. A plenary lecture will summarize major new findings and provide a theoretical basis for future investigations. The goal of the meeting is to bring together researchers studying these problems at the neuromuscular junction with those whose efforts are now focussed on the central nervous system. In each session, studies at the neuromuscular junction will introduce the problem and will then be followed by analogous studies in the central nervous system. This arrangement will both emphasize the unique access of the neuromuscular junction to experimental manipulation and challenge us to address in the brain those aspects of synaptic transmission that might be unique to the central nervous system.